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Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation

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Tomokazu Murakawa, Osamu Yamaguchi, Ayako Hashimoto, Shungo Hikoso, Toshihiro Takeda, Takafumi Oka, Hiroki Yasui, Hiromichi Ueda, Yasuhiro Akazawa, Hiroyuki Nakayama, Manabu Taneike, Tomofumi Misaka, Shigemiki Omiya, Ajay M Shah, Akitsugu Yamamoto, Kazuhiko Nishida, Yoshinori Ohsumi, Koji Okamoto, Yasushi Sakata, Kinya Otsu

Original languageEnglish
Article number7527
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Volume6
Issue number1
Early online date6 Jul 2015
DOIs
Accepted/In press16 May 2015
E-pub ahead of print6 Jul 2015
Published6 Jul 2015

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Abstract

Damaged mitochondria are removed by mitophagy. Although Atg32 is essential for mitophagy in yeast, no Atg32 homologue has been identified in mammalian cells. Here, we show that Bcl-2-like protein 13 (Bcl2-L-13) induces mitochondrial fragmentation and mitophagy in mammalian cells. First, we hypothesized that unidentified mammalian mitophagy receptors would share molecular features of Atg32. By screening the public protein database for Atg32 homologues, we identify Bcl2-L-13. Bcl2-L-13 binds to LC3 through the WXXI motif and induces mitochondrial fragmentation and mitophagy in HEK293 cells. In Bcl2-L-13, the BH domains are important for the fragmentation, while the WXXI motif facilitates mitophagy. Bcl2-L-13 induces mitochondrial fragmentation in the absence of Drp1, while it induces mitophagy in Parkin-deficient cells. Knockdown of Bcl2-L-13 attenuates mitochondrial damage-induced fragmentation and mitophagy. Bcl2-L-13 induces mitophagy in Atg32-deficient yeast cells. Induction and/or phosphorylation of Bcl2-L-13 may regulate its activity. Our findings offer insights into mitochondrial quality control in mammalian cells.

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